Eisen M B, Wiley D C, Karplus M, Hubbard R E
Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts 02138.
Proteins. 1994 Jul;19(3):199-221. doi: 10.1002/prot.340190305.
A program (HOOK) is described for generating potential ligands that satisfy the chemical and steric requirements of the binding region of a macromolecule. Functional group sites with defined positions and orientations are derived from known ligand structures or the multicopy simulation search (MCSS) method (Miranker, A., Karplus, M. Proteins 11:29-34, 1991). HOOK places molecular "skeletons" from a database into the protein binding region by making bonds between sites ("hooks") on the skeleton and functional groups. The nonpolar interactions with the binding region of candidate molecules are assessed by use of a simplified van der Waals potential. The method is illustrated by constructing ligands for the sialic acid binding site of the hemagglutinin from the influenza A virus and the active site of chloramphenicol acetyltransferase. Aspects of the HOOK program that lead to a highly efficient search of 10(5) or more skeletons for binding to 10(2) or more functional group minima are outlined.
描述了一种程序（HOOK），用于生成满足大分子结合区域化学和空间要求的潜在配体。具有确定位置和取向的官能团位点源自已知配体结构或多重复模拟搜索（MCSS）方法（米兰克，A.，卡尔普斯，M.《蛋白质》11:29 - 34，1991）。HOOK通过在骨架上的位点（“钩子”）与官能团之间形成键，将数据库中的分子“骨架”放置到蛋白质结合区域。利用简化的范德华势评估候选分子与结合区域的非极性相互作用。通过构建甲型流感病毒血凝素的唾液酸结合位点和氯霉素乙酰转移酶活性位点的配体来说明该方法。概述了HOOK程序中能够高效搜索10⁵个或更多骨架以结合到10²个或更多官能团极小值的方面。
